Bioinformatic identification of novel early stress response genes in rodent models of lung injury

摘要: Acute lung injury is a complex illness with high mortality rate (>30%) and often requires the use of mechanical ventilatory support for respiratory failure. Mechanical ventilation can lead to clinical deterioration due augmented in certain patients, suggesting potential existence genetic susceptibility stretch (6, 48), nature which remains unclear. To identify genes affected by ventilator-induced (VILI), we utilized bioinformatic-intense candidate gene approach examined expression profiles from rodent VILI models (mouse rat) using oligonucleotide microarray platform. increase statistical power analysis, 2,769 mouse/rat orthologous identified on RG_U34A MG_U74Av2 arrays were simultaneously analyzed significance analysis microarrays (SAM). This combined ortholog/SAM 41 up- 7 downregulated VILI-related genes, results validated comparable levels obtained either real-time or relative RT-PCR 15 randomly selected genes. K-mean clustering 48 clustered several well-known VILI-associated (IL-6, plasminogen activator inhibitor type 1, CCL-2, cyclooxygenase-2) number stress-related (Myc, Cyr61, Socs3). The only unannotated member this cluster (n = 14) was RIKEN_1300002F13 EST, an ortholog Gene33/Mig-6 gene. further evaluation strongly suggested its involvement development VILI. We speculate that ortholog-SAM useful, time- resource-efficient tool identification variety disease such as